scholarly journals To establish bioequivalence of 50mg Metoprolol Succinate extended release tablets in normal, healthy, adult, human subject under fasting condition

2021 ◽  
Vol 11 (1) ◽  
pp. 48-59
Author(s):  
Mahavir Singh ◽  
Lalit Singh Ranawat
Keyword(s):  
Drug Delivery ◽  
Extended Release ◽  
Healthy Adult ◽  
Reference Product ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
Test Product ◽  
Adult Human ◽  
Fasting Condition ◽  
T1 And T2

Oral drug delivery is the most preferred route for the various drug molecules among all other routes of drug delivery, because ease of administration which lead to better patient compliance. So, oral extended release drug delivery system becomes a very promising approach for those drugs that are given orally but having the shorter half-life and high dosing frequency. Extended release Extended-release systems allow for the drug to be released over prolonged time periods. By extending the release profile of a drug, the frequency of dosing can be reduced. The study was an open label, balanced, randomized, three-treatment, three-period, three-sequence, single oral dose, crossover, bioequivalence study in normal healthy adult human subjects under fasting condition, with a screening period of 28 days prior to IMP administration in Period-I. In each study period, 27 blood samples, including one pre-dose blood sample, were collected from each subject except for the discontinued / withdrawn subjects to analyze the pharmacokinetic profile of the two test products (T1 and T2) as well as the reference product. The pharmacokinetic parameters were calculated from the plasma concentration vs. time profile by non-compartmental model using Phoenix® WinNonlin® Version 6.4 (Certara L.P.) for Metoprolol. Out of 18 subjects enrolled, data of 13 subjects were analyzed. Mean Cmax is 31.634 ± 22.6007 ng/mL, 31.241 ± 20.6090 ng/mL and 31.773 ± 23.1819 ng/mL, mean AUCo-t is722.992 ± 584.3793 ng hr/mL, 658.192 ± 492.3416 ng hr/mL and 706.219 ± 546.5064 ng hr/mL, mean AUC0-inf is 751.204 ± 631.9623 ng hr/mL, 676.939 ± 519.1306 ng hr/mL and729.505 ± 578.1691 ng hr/mL for test product (T1), test product (T2) and reference product (R).Test Products (T1 and T2) when compared with the Reference Product-R meets the bioequivalence criteria with respect to Cmax, AUC0-t and AUC0-∞ for Metoprolol under fasting condition as per criteria set in the protocol.

scholarly journals BIOEQUIVALENCE STUDY OF AZELNIDIPINE 16 MG TABLET TO EVALUATE PHARMACOKINETIC PROFILE OF SINGLE DOSE IN HEALTHY, ADULT, HUMAN VOLUNTEERS UNDER FASTING CONDITION

2021 ◽  
pp. 154-159
Author(s):  
DIBYA DAS ◽  
DHIMAN HALDER ◽  
ANIRBANDEEP BOSE ◽  
CHIRANJIT SAHA ◽  
HIMANGSHU SEKHAR MAJI ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Plasma Sample ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Entire Study ◽  
Test Product ◽  
Fasting Condition

Objective: The present study's objective is to conduct a comparative bioavailability study with a special emphasis on the test product's bioequivalence using a standard reference product as a comparator. Methods: Before initiating the bioequivalent study, the plasma sample analysis method was developed and validated by using LC-MS/MS method. The entire study was conducted as a single-dose crossover randomized bioequivalence study with open-label, two treatment, two-period, and two sequences on 24 healthy volunteers under fasting condition. With proper informed consent process the oral dose of the Reference product (R) or Test product (T) was administered on healthy volunteers at 0 h during each period of the study. After the drug's oral administration, a certain quantity of blood sample was collected, and the plasma sample was separated using a cold centrifuge. The plasma samples were analysed by using the validated LC-MS/MS method. The pharmacokinetic parameters, statistical data and ANOVA of the test and reference product were evaluated. Results: The Cmax, Auc0-t, AUC0-∞ and tmax of the test product were found to be 6.29 ng/ml, 117.0 ng. h/ml, 161.67 ng. h/ml and 3.33 h. respectively. And the Cmax, Auc0-t, AUC0-∞ and tmax of reference product were found 6.59 ng/ml, 123.21 ng. h./ml, 172.20 ng. h/ml and 3.38 h respectively. Relative bioavailability was found 94.96%. The overall results show that the 90% confidence intervals (Log-Transformed and Untransformed) for Cmax, AUC0-t and AUC0-∞ for Azelnidipine were within the acceptable limit of 80%-125%. Conclusion: The entire study's conclusion can be drawn as the test product was bioequivalent with the reference product's comparator.

scholarly journals Preparation of Nifedipine Push-Pull Osmotic Pump Tablets

2020 ◽  
Vol 36 (4) ◽  
Author(s):  
Tran Quang Trung ◽  
Nguyen Thi Dao ◽  
Nguyen Thanh Hai ◽  
Trinh Van Lau
Keyword(s):  
Drug Delivery ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
The United States ◽  
Osmotic Pump ◽  
Oral Drug ◽  
Drug Formulary ◽  
National Drug ◽  
Osmotic Agent ◽  
Formulation Factors

This study aims to investigate the influence of the formulation factors on the drug release kinetics, thereby selecting the compositions of extended-release nifedipine tablet based on the similarity coefficient f2 obtained when compared with Adalat LA tablet. The formulation factors such as: molecular weight of the polyethylene oxide (PEO) and osmotic agent amount in drug layer and push layer, semi permeable membrane thickness (estimated by coating weight gain), orifice size, type of plasticizers and ratios of coating polymer to plasticizer in semipermeable membrane were evaluated. It was found that developed tablets were able to deliver nifedipine in an approximate zero-order manner up to 20 hours and drug release profile of developed tablets was similar to that from Adalat LA tablets. The developed tablet contained: PEO N10, PEO 303 in drug layer and push layer, respectively; percentages of osmotic agent in drug layer and push layer were 10% and 30%, respectively; weight gain of semipermeable coating was 12%; and orifice size was 0.8 mm. Keywords  Nifedipine, GPKD, push-pull osmotic pump, PEO, Tlag. References [1] Vietnamese National Drug Formulary Council, Nifedipine, Vietnamese National Drug Formulary, 2nd edition, Medical Publising House, Hanoi, 2018, pp. 1056-1058 (in Vietnamese).[2] A. Nokhodchi, M.N. Momin, J. Shokri, et al., Factors affecting the release of nifedipine from a swellable elementary osmotic pump, Drug Delivery, 15 (1) (2008) 43-48. https://doi.org/10.1080/10717540701829028[3] R.K. Verma, D.M. Krishna, S. Garg, Formulation aspects in the development of osmotically controlled oral drug delivery systems, Journal of controlled release 79 (1-3) (2002) 7-27. https://doi.org/10.1016/s0168-3659(01)00550-8.[4] The United States Pharmacopeial Convention, Nifedipine Extended-Release Tablets, The United States Pharmacopeia, 41st edition, United Book Press, Baltimore, 2018, pp. 2938 - 2944.[5] V. Malaterre, J. Ogorka, N. Loggia, et al., Approach to design push–pull osmotic pumps, International Journal of Pharmaceutics 376 (1–2) (2009) 56-62. http://dx.doi.org/10.1016/j.ijpharm.2009.04.015.[6] S. Missaghi, P. Patel P, Farrell T. P., et al., Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery, AAPS PharmSciTech 15 (1) (2014) 149-160. http://doi.org/10.1208/s12249-013-0040-4.[7] V. Malaterre, H. Metz, J. Ogorka , et al., Benchtop-magnetic resonance imaging (BT-MRI) characterization of push-pull osmotic controlled release systems, J Control Release 133 (1) (2009) 31-36. http://doi.org/10.1016/j.jconrel.2008.09.007.[8] Z. Zhang, W. Li, S. Nie, et al., Overcome side identification in PPOP by making orifices on both layers, International journal of pharmaceutics 371 (1-2) (2009) 1-7. http://dx.doi.org/10.1016/j.ijpharm.2008.12.006[9] C. Wu, Z. Zhao, Y. Zhao, et al., Preparation of a push–pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core–shell structure, International Journal of Pharmaceutics,475 (1-2) (2014) 298 - 305 . http://dx.doi.org/10.1016/j.ijpharm.2014.08.033.[10] V. Patel, A. Chudasama, M. Nivsarkar, et al., Push-pull osmotic pump for zero order delivery of lithium carbonate: Development and in vitro characterization, Pharmaceutical development and technology, 17 (3) (2012) 375-382. http://doi.org/10.3109/10837450.2010.542577.[11] C.N. Patra, S. Swain, J. Sruti, et al., Osmotic drug delivery systems: Basics and design approaches, Recent Patents on Drug Delivery & Formulation 7(2) (2013) 1 - 12. http://doi.org/10.2174/1872211311307020007.    

scholarly journals A Review Extended Release Oral Drug Delivery System and Multiparticulate Drug Delivery Systems (MDDS)

2020 ◽  
pp. 84-92
Author(s):  
Swapnil B. Khambat ◽  
Shubham A. Kale.
Keyword(s):  
Drug Delivery ◽  
Dosage Form ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
Oral Dosage ◽  
Oral Drug ◽  
Solid Dosage ◽  
Oral Formulations ◽  
Oral Drug Delivery System ◽  
Oral Dosage Forms

The extended release product will optimize therapeutic effect and safety of a drug at the same time improving the patient convenience and compliance. By incorporating the dose for 24 hrs into one tablet/capsule from which the drug is released slowly. The concept of multiple unit dosage form was initially introduced in the early 1950’s.These forms play a major role in the design of solid dosage form processes because of their unique properties and the flexibility found in their manufacture. These forms can be defined as oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. The release of drug from pellets depends on a variety of factors including the carrier used to form pellets and the amount of drug contained in them. Consequently, pellets provide tremendous opportunities for designing new controlled and extended release oral formulations, thus extending the frontier of future pharmaceutical development. The possible mechanism for drug release includes solution/diffusion through the continuous polymer phase or plasticizer channels, diffusion through aqueous pores and osmotically driven release through aqueous pores. To distinguish between these mechanisms, the release rate was studied as a function of coating thickness, plasticizer content and osmotic pressure in the dissolution medium.

scholarly journals Oral multiunit pellet extended release dosage form: A review

2013 ◽  
Vol 2 (10) ◽  
pp. 177-184 ◽  
Author(s):  
Vishal Sachdeva ◽  
Md. Shoaib Alam ◽  
Ramesh Kumar ◽  
Mahesh Kumar Kataria
Keyword(s):  
Drug Delivery ◽  
Extended Release ◽  
Oral Drug Delivery ◽  
Pharmaceutical Journal ◽  
Oral Drug ◽  
Gastric Residence Time ◽  
Drug Molecules ◽  
Oral Formulations ◽  
Dosing Frequency ◽  
Recent Trends

Oral drug delivery is the most preferred route for the various drug molecules among all other routes of drug delivery, because ease of administration which lead to better patient compliance. So, oral extended release drug delivery system becomes a very promising approach for those drugs that are given orally but having the shorter half-life and high dosing frequency. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving extended release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. The release of drug from pellets depends on a variety of factors including the carrier used to form pellets and the amount of drug contained in them. Consequently, pellets provide tremendous opportunities for designing new controlled and extended release oral formulations, thus extending the frontier of future pharmaceutical development.DOI: http://dx.doi.org/10.3329/icpj.v2i10.16413 International Current Pharmaceutical Journal, September 2013, 2(10): 177-184

scholarly journals Current State-of-Art and New Trends on Lipid Nanoparticles (SLN and NLC) for Oral Drug Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Patrícia Severino ◽  
Tatiana Andreani ◽  
Ana Sofia Macedo ◽  
Joana F. Fangueiro ◽  
Maria Helena A. Santana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Oral Drug Delivery ◽  
Lipid Nanoparticles ◽  
Oral Route ◽  
Delivery Systems ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
Drug Molecules ◽  
Current State

Lipids and lipid nanoparticles are extensively employed as oral-delivery systems for drugs and other active ingredients. These have been exploited for many features in the field of pharmaceutical technology. Lipids usually enhance drug absorption in the gastrointestinal tract (GIT), and when formulated as nanoparticles, these molecules improve mucosal adhesion due to small particle size and increasing their GIT residence time. In addition, lipid nanoparticles may also protect the loaded drugs from chemical and enzymatic degradation and gradually release drug molecules from the lipid matrix into blood, resulting in improved therapeutic profiles compared to free drug. Therefore, due to their physiological and biodegradable properties, lipid molecules may decrease adverse side effects and chronic toxicity of the drug-delivery systems when compared to other of polymeric nature. This paper highlights the importance of lipid nanoparticles to modify the release profile and the pharmacokinetic parameters of drugs when administrated through oral route.

scholarly journals The Statistical Analysis of Pharmacokinetic Parameters in the Context of Bioequivalence Testing of Two Anthelmintic Formulas Based on Ivermectine and Triclabendazole in Sheep

2019 ◽  
Vol 65 (2) ◽  
pp. 60-65
Author(s):  
Lenard Farczadi ◽  
Laurian Vlase ◽  
Orsolya Melles ◽  
Ramona Tolomeiu ◽  
Octavia Tamas-Krumpe ◽  
...  
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Plasma Concentrations ◽  
Pharmaceutical Formulations ◽  
Relative Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Test Product

AbstractConducting bioequivalence studies is an essential step during the market authorization process of generic pharmaceutical formulations, for both human or veterinary use. The aim of the present study was to evaluate the pharmacokinetics of triclabendazole sulphoxide, the main metabolite of triclabendazole, and ivermectin in order to evaluate the bioavailability and bioequivalence of a novel sheep anthelmintic formulation of oral suspension for sheep treatment containing triclabendazole 50 mg/mL and ivermectin 1 mg/mL compared to the reference product. In order to determine relative bioavailability of the test product with respect to the reference product the study was conducted on 36 clinically healthy sheep, following an unicentric, randomized, cross-over, two-sequence, two-treatment and 14-day wash-out study design. For the determination of triclabendazole sulphoxide and ivermectin sheep plasma concentrations, two rapid, selective high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) methods were developed and validated. The measured plasma concentrations of triclabendazole sulphoxide and ivermectin were used for the pharmacokinetic analysis and the determination of bioequivalence between the test product with regards to the reference product. The noncompartmental analysis of the pharmacokinetic data for both triclabendazole sulphoxide and ivermectin showed similarities between first-order kinetics of the test and reference product. The relevant pharmacokinetic parameters (Cmax, AUClast, AUCtot) were determined and the bioequivalence between the test and reference product could be concluded.

scholarly journals Bioequivalence Study of Donepezil Hydrochloride Tablets in Healthy Male Volunteers

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Noppamas Rojanasthien ◽  
Siriluk Aunmuang ◽  
Nutthiya Hanprasertpong ◽  
Sukit Roongapinun ◽  
Supanimit Teekachunhatean
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Two Phase ◽  
Test Product ◽  
Male Volunteers ◽  
Bioequivalence Range ◽  
The Mean ◽  
The Difference

The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0–∞ and were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0–∞ and values of the test product over those of the reference product were 1.08 (1.02–1.14) and 1.08 (0.99–1.17), respectively (within the bioequivalence range of 0.8–1.25). The median for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the difference between the two preparations was –0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the of the reference formulation. Our study demonstrated the bioequivalence of the two preparations.

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